NM_012301.4:c.419-102800C>T

Variant names:

• chr7-78730039-G-A
• rs10242163
• NM_012301.4:c.419-102800C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.419-102800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,938 control chromosomes in the GnomAD database, including 10,971 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10971 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 3 publications found

Genes affected

MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

MAGI2 Gene-Disease associations (from GenCC):

• nephrotic syndrome 15

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-102800C>T		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-102800C>T		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56634 AN: 151820 Hom.: 10959 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56670 AN: 151938 Hom.: 10971 Cov.: 31 AF XY: 0.367 AC XY: 27277 AN XY: 74262

African (AFR) AF: 0.293 AC: 12118 AN: 41416

American (AMR) AF: 0.374 AC: 5718 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1559 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1516 AN: 5162

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4820

European-Finnish (FIN) AF: 0.360 AC: 3797 AN: 10544

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.432 AC: 29378 AN: 67948

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.412 Hom.: 47094

Bravo AF: 0.375

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.46
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10242163; hg19: chr7-78359355;